Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks

被引：607

作者：

Sedelnikova, OA

Horikawa, I

Zimonjic, DB

Popescu, NC

Bonner, WM ^{[1
]}

Barrett, JC

机构：

[1] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[2] NCI, Lab Biosyst & Canc, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[3] NCI, Lab Expt Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

来源：

NATURE CELL BIOLOGY | 2004年 / 6卷 / 02期

关键词：

D O I：

10.1038/ncb1095

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Humans and animals undergo ageing, and although their primary cells undergo cellular senescence in culture, the relationship between these two processes is unclear(1,2). Here we show that gamma-H2AX foci (gamma-foci), which reveal DNA double-strand breaks (DSBs)(3,4), accumulate in senescing human cell cultures and in ageing mice. They colocalize with DSB repair factors, but not significantly with telomeres. These cryptogenic gamma-foci remain after repair of radiation-induced gamma-foci, suggesting that they may represent DNA lesions with unrepairable DSBs. Thus, we conclude that accumulation of unrepairable DSBs may have a causal role in mammalian ageing.

引用

页码：168 / +

页数：4

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